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Reperfusion after hypoxia-ischemia exacerbates brain injury with compensatory activation of the antiferroptosis system:based on a novel rat model

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Neural Regeneration Research 2023年第10期18卷 2229-2236页

作者： Tian-Lei Zhang Zhi-Wei Zhang Wei Lin Xin-Ru Lin Ke-Xin Lin Ming-Chu Fang Jiang-Hu Zhu Xiao-Ling Guo Zhen-Lang Lin Department of Pediatrics the Second School of Medicinethe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Second Clinical Medical College Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Key Laboratory of Children Genitourinary Diseases of Wenzhou the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Key Laboratory of Perinatal Medicine of Wenzhou the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Basic Medical Research Center the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina

Hypoxic-ischemic encephalopathy,which predisposes to neonatal death and neurological sequelae,has a high morbidity,but there is still a lack of effective prevention and treatment in clinical *** better understand the pathophysiological mechanism underlying hypoxic-ischemic encephalopathy,in this study we compared hypoxic-ischemic reperfusion brain injury and simple hypoxic-ischemic brain injury in neonatal ***,based on the conventional ricevannucci model of hypoxic-ischemic encephalopathy,we established a rat model of hypoxic-ischemic reperfusion brain injury by creating a common carotid artery muscle *** we performed tandem mass tag-based proteomic analysis to identify differentially expressed proteins between the hypoxic-ischemic reperfusion brain injury model and the conventional rice-vannucci model and found that the majority were mitochondrial *** also performed transmission electron microscopy and found typical characteristics of ferroptosis,including mitochondrial shrinkage,ruptured mitochondrial membranes,and reduced or absent mitochondrial ***,both rat models showed high levels of glial fibrillary acidic protein and low levels of myelin basic protein,which are biological indicators of hypoxic-ischemic brain injury and indicate similar degrees of ***,we found that ferroptosis-related Ferritin(Fth1)and glutathione peroxidase 4 were expressed at higher levels in the brain tissue of rats with hypoxic-ischemic reperfusion brain injury than in rats with simple hypoxic-ischemic brain *** on these results,it appears that the rat model of hypoxic-ischemic reperfusion brain injury is more closely related to the pathophysiology of clinical *** not only aggravates hypoxic-ischemic brain injury but also activates the anti-ferroptosis system.

关键词： ferroptosis hypoxic-ischemic brain injury hypoxic-ischemic encephalopathy hypoxic-ischemic reperfusion brain injury mitochondria model proteomic analysis reperfusion rice-vannucci transmission electron microscopy

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